Systemic inflammation alters the composition of exhaled breath, possibly helping clinicians diagnose conditions such as sepsis. We therefore evaluated changes in exhaled breath of rats given tumor necrosis factor-alpha (TNF-&alpha
). Thirty male Sprague-Dawley rats were randomly assigned to three groups (n = 10 each) with intravenous injections of normal saline (control), 200 µ
g·
kg&minus
1 bodyweight TNF-&alpha
(TNF-&alpha
200), or 600 µ
600), and were observed for 24 h or until death. Animals were ventilated with highly-purified synthetic air to analyze exhaled air by multicapillary column&ndash
ion mobility spectrometry. Volatile organic compounds (VOCs) were identified from a database. We recorded blood pressure and cardiac output, along with cytokine plasma concentrations. Control rats survived the 24 h observation period, whereas mean survival time decreased to 22 h for TNF-&alpha
200 and 23 h for TNF-&alpha
600 rats. Mean arterial pressure decreased in TNF-&alpha
groups, whereas IL-6 increased, consistent with mild to moderate inflammation. Hundreds of VOCs were detected in exhalome. P-cymol increased by a factor-of-two 4 h after injection of TNF-&alpha
600 compared to the control and TNF-&alpha
200. We found that 1-butanol and 1-pentanol increased in both TNF-&alpha
groups after 20 h compared to the control. As breath analysis distinguishes between two doses of TNF-&alpha
and none, we conclude that it might help clinicians identify systemic inflammation.